3. Associated symptoms: mood change is associated with other non-mood symptoms (referred to “neurovegetative” symptoms because they include changes in body function) – e.g., changes in sleep, attention/concentration, etc.

4. Functional impairment: mood change interferes with child’s functioning at home/family, at school, and with peers.

Major depressive disorder (MDD):

A. Having at least 1 major depressive episode (MDE) consisting of 5 or more of the following symptoms during the same 2-week (or more) period [including either #1 or #2]:

Depressed mood most of the day, nearly every day (Note: in children, DSM-5 allows this to be “irritable” mood, although as above in first paragraph, depressed or irritable mood needs to be a change from their usual mood. If they are chronically/always irritable, you need to consider another disorder – see below.).

Decreased interest/pleasure in most activities most of the day, nearly every day.

C. Symptoms not directly due to substance use/abuse or medical condition.

D. Can never have had manic or hypomanic episode or psychotic disorder (e.g., schizophrenia).

Persistent depressive disorder (dysthymia):

A. Depressed mood, most of the day, more days than not, for >1 year (children) or >2 years (adults). (Note: children’s mood can be irritable)

B. >2 of the following:

Decreased or increased appetite.

Insomnia or hyposomnia.

Fatigue/low energy.

Decreased self-esteem.

Indecision/decreased concentration.

Hopelessness.

C. No major depressive episode during first 2 years of dysthymic disorder (1 year in children).

D. No manic/hypomanic episode or psychotic disorder.

E. Not due to substance use/abuse or medical condition.

Disruptive mood dysregulation disorder:

Disruptive mood dysregulation disorder (DMDD) is a new diagnosis in DSM-5 based on more than 15 years of research designed to address key issues in pediatric bipolar disorder, namely are children with chronic, non-episodic irritability the same or different than children with distinct episodes of euphoric mania, including examination of longitudinal symptom trajectory from childhood to adulthood and neuroimaging findings.

Most importantly, DMDD is not meant to be a replacement for a “mood disorder not otherwise specified” that was eliminated in DSM-5. In particular, DMDD is meant to be among the most specific disorders in DSM-5 and is not a “catch all” for children with irritability. As below – criteria J – DMDD should not be used when children actually have bipolar disorder or autism spectrum disorder or other condition that better explains the chronic irritability.

DMDD is placed in the “depression” section of DSM-5 because those studies suggest that children with DMDD are at high risk of developing major depressive disorder when they are adults (rather than an elevated risk for bipolar disorder).

Important changes in the diagnostic criteria for bipolar disorder moving from DSM-IV to DSM-5 include:

(1) the euphoric or irritable mood change as part of bipolar disorder must be present most of the day, nearly every day (or any duration if hospitalization is necessary) mirroring language from a major depressive episode;

(2) either increased goal-directed activity or energy must also be present during the manic episode;

(3) the former “bipolar disorder not otherwise specified” has been split into two disorders:

“other specified bipolar disorder” (for patients with symptoms of bipolar disorder that cause distress/impairment, but do not meet full criteria for type I or II; e.g., someone with a 2-3 day full criteria except duration mania);

Of those with depression, 10-20% may develop bipolar disorder. Bipolar disorder prevalence ~3-5% of adult population (1/3 adults with bipolar disorder report onset of mania/hypomania prior to age 21 years).

Genetics: No single gene for depression or bipolar disorder. Increased risk among first-degree relatives; however, children with bipolar disorder more likely to have first-degree relative with major depression rather than bipolar disorder.

Sleep/circadian rhythm: Sleep deprivation is a known trigger for mania.

Family environment: Maternal depression strongly linked to onset of child depression and other psychiatric disorders. Family discord and elevated expressed emotion also linked to depression. Inter-personal conflict (i.e., fights with child peers or adolescent romantic relationships) also triggers for depression and/or suicide).

Stress: Stressful life events may be related to onset of depression and bipolar disorder.

Neuroendocrine: Hypothalamic-pituitary-adrenal (HPA) axis dysfunction may be related to depression, though some data in children is mixed.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

If indicated, it may be useful to evaluate TSH/free T4 (thyroid dysfunction), CBC+diff (heme), BMP (eating disorders), or toxicology screen (though many report adolescents fully disclose their use if asked non-judgementally).

Rating scales: Rating scales/questionnaires can be very helpful to clarify the diagnosis/severity of depression or co-occurring issues.

Would imaging studies be helpful? If so, which ones?

Not generally indicated unless strong suspicion of medical issues (e.g., early morning headaches/vomiting – suggestive of cerebral tumor rather than primary depression) or associated psychosis that is not mood-congruent (e.g., seems disconnected with psychiatric symptoms) or does not improve with treatment of underlying mood disorder.

Selection of which SSRI should be guided by first-degree relative positive or negative response and at present typically starts with any of these agents: fluoxetine (Prozac), sertraline (Zoloft), or citalopram (Celexa).

Use of SSRIs must also include a discussion of the FDA black box warning on anti-depressant/anti-anxiety serotonergic agents including SSRIs in any patient <25 years old (see www.fda.gov).

Medication treatment also requires close monitoring for treatment emergent side effects, including suicidality or mania, especially during the first 12 weeks. Many suggest this should include weekly check-ins (can be face-to-face or alternating with telephone contact) for the first 8-10 weeks, then gradually spaced out.

Use of dextromethorphan containing agents (i.e., cough suppressants) is contra-indicated with concomitant SSRI use due to increased risk for serotonin syndrome, including irritability and rage.

Term “mood stabilizer” should not be used as this is purely a marketing term coined by the pharmaceutical industry creating artificial expectations.

Psychotherapy:

Can involve psychoeducation or CBT (see above in “depression”) or:

Family-focussed therapy (FFT): Combines elements of psychoeducation and CBT administered to families and is highly effective for pediatric bipolar disorder.

Interpersonal social rhythm therapy (IPSRT): Focuses on maintaining regular sleep, exercise, diet, and social contact to avoid mania and depression and also, if those become irregular, to recognize that these may be warning signs of impending manic or depressive episode.

Long-term: For depression, some (but not all) children/adolescents find after 1 year of treatment, it is possible to gradually taper to discontinuation their medications without recurrence/re-emergence of symptoms. For bipolar disorder, this is often a life-long condition, requiring careful adjustment of medication to meet a patient’s symptoms as they grow/develop.

Other clinical manifestations that might help with diagnosis and management

Some say up to 20% of those initially presenting with depression may develop bipolar disorder. So, cautious monitoring for development of mania is warranted in anyone treated for depression.

What complications might you expect from the disease or treatment of the disease?

Depression: With time, some people who have responded to a certain anti-depressant may see their depression worse/re-emerge. The cause is unknown, but it may require dose adjustment, augmentation with another anti-depressant, or switch to another anti-depressant.

Bipolar disorder: As above, careful monitoring is required to meet the goals of minimizing/preventing mania or depression, while addressing co-occurring psychiatric disorders, and monitoring/treating any potential side effects of these medications (metabolic syndrome, thyroid dysfunction, etc.).

Are additional laboratory studies available; even some that are not widely available?

Despite many claims made on the internet, there is no gene or brain scan that can reliably diagnose either depression or bipolar disorder in children, adolescents, or adults.

How can mood disorders be prevented?

At this time, there is no primary prevention for either depression or bipolar disorder. Children of parents with either condition should be screened periodically, though it is not a 1:1 correspondence of parent with mood disorder = child with mood disorder.

Ongoing controversies regarding etiology, diagnosis, treatment

Depression: Current research focused on: (a) bio-behavioral predictors of diagnosis and treatment response, (b) best practices for medication and therapy treatments, (c) improving access to currently available treatments, (d) identifying new treatments, especially novel medications.

Bipolar disorder: Controversial with regard to diagnosis – including how to establish the diagnosis (or rule it out) taking into account issues of development (i.e., distinguishing it from normal mood fluctuations or temper tantrums), and other psychiatric disorders (e.g., ADHD, anxiety, autism-spectrum disorders), and the new DSM-5 DMDD.

Current research focussed on increasing diagnostic specificity using both interviews, mood charting, questionnaires, and bio-behavioral markers. Using both cross-sectional and longitudinal data.

Also work akin to that in depression – i.e., (a) bio-behavioral predictors of diagnosis and treatment response, (b) best practices for medication and therapy treatments, (c) improving access to currently available treatments, (d) identifying new treatments, especially novel medications.